The NDA acceptance is based on positive results from the KRYSTAL-1 trial, which looked into the effect of using 600mg BID of adagrasib in patients.
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The U.S. Food and Drug Administration has accepted Mirati Therapeutics’ New Drug Application (NDA) for its candidate drug for non-small cell lung cancer (NSCLC).
The NDA for adagrasib, an investigational, highly selective and potent oral small-molecule inhibitor of KRASG12C optimized to sustain target inhibition, was placed under FDA review for Accelerated Approval (Subpart H). Not the fastest-possible three-month review, the drug’s Prescription Drug User Free Action (PDUFA) date is December 14, 2022.
The NDA acceptance is based on positive results from the Phase II KRYSTAL-1 trial, which looked into the effect of using 600mg BID of adagrasib in patients with advanced NSCLC harboring KRASG12C mutations after they already received chemotherapy and immunotherapy either sequentially or together.
The study specifically involved patients with pretreated ductal adenocarcinoma and other gastrointestinal tumors that carry a mutation, including cancers of the appendix, small bowel, biliary tract, esophagus and gastro-esophageal junction. Topline results from this study were reported in September 2021. The company expects to publish more details at a yet-to-be-announced medical conference in the first half of 2022.
“New clinical data presented at ASCO GI show that adagrasib, an inhibitor of KRASG12C, demonstrated promising clinical activity in patients with pancreatic cancer and other GI tumors. These findings build on the previously reported positive adagrasib clinical data in colorectal and pancreatic cancers, and are highly encouraging, warranting further investigation of adagrasib in this setting,” commented Dr. Tanois S. Bekaii-Saab, an investigator of the KRYSTAL-1 study, in an earlier statement.
Adagrasib’s effect is significant to treating KRASG12C-mutated cancers as the protein has the ability to regenerate in 24 to 48 hours. The drug is being evaluated for monotherapy or other treatments in patients with advanced mutated solid tumors such as NSCLC, pancreatic cancer and colorectal cancer.
In addition to the FDA accelerated approval review, adagrasib is being evaluated under the FDA’s Real-Time Oncology Review pilot program, which focuses on the immediate delivery of safe and effective treatments to cancer patients. The drug already holds a Breakthrough Therapy Designation in the U.S. for people diagnosed with NSCLC with a KRASG12C mutation and have received at least one systemic treatment before.
Mirati also holds an expanded access program (EAP) to treat eligible patients with KRASG12C mutated cancers regardless of the tumor type.
“KRAS mutations have been notoriously hard to target and historically have had limited therapeutic options. The KRASG12C biomarker in particular is associated with poor survival outcomes. The FDA’s review of the adagrasib NDA marks important progress toward potentially providing a new, targeted option for those living with KRASG12C-mutated non-small cell lung cancer,” said Pasi A. Jänne, M.D., Ph.D, director of the Lowe Center for Thoracic Oncology and another of the investigators in the KRYSTAL-1 trial.
Mirati is also conducting a confirmatory Phase III study, called KRYSTAL-12, which assesses the drug against docetaxel in patients with second-line KRASG12C-mutated NSCLC. The company may provide more information on its pipeline items on February 28, when it announces its financial results for the fourth quarter and the full year of 2021.
